title: miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor.
abstract: OBJECTIVE
  miR-181a expression is frequently altered in different types of cancer. Members of the Wnt/β-catenin signalling pathway, which is commonly altered in colorectal cancer (CRC), have been reported as molecular interaction partners of miR-181. However, the role of miR-181a expression in CRC and its ability to predict survival and response to agents targeting the epidermal growth factor receptor (EGFR) have not been explored yet.
  
  
  METHODS
  In this study, we analysed 80 patients with wild type KRAS CRC undergoing treatment with the EGFR-targeting monoclonal antibodies cetuximab and panitumumab for metastatic CRC. The KRAS mutational status was determined by pyrosequencing and miR-181a expression was measured by quantitative RT-PCR in CRC tumour tissue and corresponding non-neoplastic colon tissue. The microRNA expression levels were correlated with clinicopathological characteristics. Cancer-specific survival was calculated by univariate and multivariate analyses, and progression-free survival (PFS) during treatment with EGFR-targeting agents was also evaluated.
  
  
  RESULTS
  A low miR-181a expression level was associated with poor differentiation of CRC (p=0.04). A Kaplan-Meier curve showed a decreased survival time for patients with low miR-181a expression (p=0.019). Low miR-181a expression was furthermore associated with poor PFS (p=0.015).
  
  
  CONCLUSIONS
  In conclusion, our data suggest that the miR-181a expression level is associated with poor survival in patients with CRC. Furthermore, miR-181a expression might predict PFS in EGFR-targeted therapy.
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), , Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.forename: Elke
authors.initials: E
authors.lastname: Winter
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Ress
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauernhofer
authors.forename: Armin
authors.initials: A
authors.lastname: Gerger
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lax
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002454:Cell Differentiation; D000068818:Cetuximab; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D009154:Mutation; D000077544:Panitumumab; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab
keywords: CANCER; CANCER RESEARCH; COLORECTAL CANCER